Management of patients with acute myeloid leukemia undergoing therapy with midostaurin: a focus on antifungal prophylaxis

Both therapy and prophylaxis for infectious complications during the treatment of acute myeloid leukemia (AML) have improved, although invasive fungal disease still remains a life-threatening occurrence. Accordingly, prophylactic strategies with effective and well-tolerated antifungals remain a cornerstone of management. Herein, the recent literature on antifungal prophylaxis used during the treatment of AML is reviewed, with a focus on the use in combination with midostaurin. The multikinase inhibitor midostaurin targets FMS-like tyrosine kinase 3 (FLT3) and is approved, in association with 7 + 3, for the treatment of adult patients with newly diagnosed FLT3-mutated AML. Midostaurin has been shown to extend both overall and event-free survival in AML patients with an FLT3 mutation and is now the standard of care in FLT3+ AML. Antifungal prophylaxis should be adopted during all phases of treatment in all AML patients, and the strong CYP3A4 inhibitor posaconazole is frequently the preferred agent. As midostaurin is metabolized primarily by CYP3A4, there is a potential for drug-drug interactions that requires further evaluation. At present, the available data suggest that there are no absolute contraindications for coadministration of midostaurin with posaconazole, albeit with cautious monitoring. Considering the survival advantage offered by midostarin, concomitant administration of strong CYP3A4 inhibitors should not be ruled out, although such use should be evaluated cautiously and used on a case-by-case basis only if there are no suitable alternatives. It should also be kept in mind that patients with invasive fungal infection undergoing therapy for AML with midostaurin may need prolonged antifungal therapy, which must be based on the administration of the appropriate antifungal agent.